Tuberculosis (TB) has resurged dramatically in recent years in the United States due in part to the AIDS epidemic. HIV-positive drug users are at particularly high risk of contracting active TB and dying of this infection. The patterns of Mycobacterium tuberculosis spread among drug users, the behavioral factors influencing dissemination, and the amount of strain "spillover" to other societal subpopulations are largely unknown, and will be studied herein. COMPREHENSIVE, POPULATION-BASED EPIDEMIOLOGIC STUDY OF VIRTUALLY ALL M. TUBERCULOSIS ISOLATES RECOVERED IN HOUSTON OVER FIVE YEARS (700 - 800 STRAINS/YEAR) WILL BE CONDUCTED BY A LARGE GROUP OF COLLABORATING INVESTIGATORS LOCATED IN THE TEXAS MEDICAL CENTER. Strain characterization will be done by state-of-the-art molecular epidemiologic techniques, including IS6110 fingerprinting, and automated DNA sequencing. One of the major hypotheses to be tested is that facilitated transmission of a limited number of clones among drug users and others is occurring in Houston. Newly-formulated strategies to study social networks among drug users and others will be employed, and (in close collaboration with Houston TB officers), the molecular and behavioral data will be used to formulate more rational and targeted prevention and control strategies. New automated DNA sequencing strategies for rapid infection diagnosis and identification of drug-resistant TB strains in primary specimens such as sputum will be developed. This population-based study will supply crucial missing information about the precise frequency of strain sharing among and between drug users and other populations, identify modifiable risk factors, facilitate a targeted approach to TB prevention among drug users, and demonstrate the feasibility of rapid mycobacterial species assignment, identification of mutations conferring antibiotic-resistance, and molecular epidemiologic studies with primary specimens such as sputum. Special attention will be devoted to identification of behavioral differences among drug users involved in TB microepidemics and those with disease caused by unique MTB strains.